Med Pediatr Oncol 2002;39:128–131

BRIEF REPORTMalignant Rhabdoid Tumor of Adrenal Gland

Nilgun Yaris, MD,1* Umit Cobanoglu, MD,2 Embiya Dilber, MD,1 Ali Ahmetoglu, MD,3

Haluk Saruhan, MD,4 and Aysenur Okten, MD1

Malignant rhabdoid tumor (MRT) is a rare pediatrictumor principally but not exclusively arising from thekidney of infants and young children. It constitutes 1.8%of malignant renal tumor and exhibits an aggressivelyinfiltrative growth pattern [1,2]. This highly aggressiveneoplasm has a poor prognosis. Histologically, MRT ischaracterized by large rhabdoid cells with eosinophiliccytoplasm containing filamentous inclusions and largevesicular nuclei with prominent nucleoli [1,2]. Ourexperience with a child with a primary rhabdoid tumorof the adrenal gland is of interest because to ourknowledge, this is the first adrenal MRT to be reported.We provide the clinical, morphologic, ultrastructural, andimmunohistochemical features.

A 3-year-old boy was admitted to hospital with a2-week history of fatigue, abdominal pain accompani-ed by respiratory distress during the previous 2 days.Physical examination demonstrated diminished breathsounds over the left hemithorax, tachypnea (60/minute),dyspnea, pallor, hepatomegaly (3 cm below the costalmargin), and a hard mass palpable in the left lumbarregion. Laboratory investigation revealed: hemoglobinlevel 8.5 g/dl, white cell count 13,400/mm3, and normaldifferential and platelet counts. Biochemical analysesincluding urinary vanillylmandelic acid and homovanillicacid levels were normal. Imaging studies of the thoraxand abdomen showed a massive left pleural effusion anda mass 10� 10 cm in diameter. It originated above theleft kidney and pushed it downwards (Fig. 1). There wereno atypical cells on the bone marrow aspirate. Thor-acentesis was performed and haemorrhagic fluid wasobtained. The clinical and radiologic findings suggestedneuroblastoma, and he underwent surgery urgently be-cause of the hemothorax. During surgery, a huge massarising from the left adrenal gland was observed. It en-compassed the midline vascular structures. The surgeonemphasized that the tumor was certainly not related toand did not invade the kidney, but had infiltrated andpenetrated the left diaphragm. A subtotal excision of thetumor was performed, the diaphragm was repaired and atube was placed in left pleural cavity. The post-operativecourse was stormy and the patient soon died of progres-

sive disease after the first course of planned multi-agentchemotherapy.1

Microscopically, non-cohesive tumor cells containedlarge vesicular nuclei with prominent nucleoli and PAS-positive large eosinophilic globular cytoplasmic inclu-sions (Fig. 2). Scattered multinucleated giant cells andnumerous mitoses were also present. Immunohistochem-ical studies showed that the tumor cells were stronglypositive for vimentin, the staining being para-nuclear andcorresponding to ‘‘inclusions’’ noted in H & E stainedsections (Fig. 3). Immunostaining also showed cytoplas-mic staining for epithelial membrane antigen (Fig. 4) andweak reactivity with cytokeratin. The cells were stainednegatively with leukocyte common antigen, CD30, S-100protein, neuron specific enolase, synaptophysin, chromo-granin, alfafetoprotein, b-HCG, desmin, and myoglobin.For electron microscopy, formalin fixed tissue was re-moved from the paraffin block, deparaffinised in xylene

Key words: rhabdoid tumor; adrenal gland neoplasms; childhood cancer

1Vincristine (1.4 mg/m2), cyclophosphamide (200 mg/m2, for 3 days),and doxorubicin (30 mg/m2, for 2 days) alternated with cisplatin(100 mg/m2) and etoposide (120 mg/m2, for 3 days).

——————1Department of Paediatric Oncology, Karadeniz Technical UniversityFaculty of Medicine, Trabzon, Turkey

2Department of Pathology, Karadeniz Technical University Faculty ofMedicine, Trabzon, Turkey

3Department of Radiology, Karadeniz Technical University Faculty ofMedicine, Trabzon, Turkey

4Department of Paediatric Surgery, Karadeniz Technical UniversityFaculty of Medicine, Trabzon, Turkey

Nilgun Yaris is an Assistant Professor of Pediatrics and PediatricOncologist. Umit Cobanoglu is an Assistant Professor of Pathology.Embiya Dilber is an Assistant Professor of Pediatrics. Aysenur Okten isan Professor of Pediatrics. Ali Ahmetoglu is an Assistant Professor ofRadiology. Haluk Saruhan is an Associated Professor of PediatricSurgery.

*Correspondence to: Nilgun Yaris, MD, Department of Paediatrics,Karadeniz Technical University, Faculty of Medicine, 61080 Trabzon,Turkey. E-mail: nyaris@meds.ktu.edu.tr

Received 29 March 2001; Accepted 13 October 2001

� 2002 Wiley-Liss, Inc.DOI 10.1002/mpo.10059

and postfixed in glutaraldehyde. Tissue was postfixed inbuffered osmium tetroxide, dehydrated in ethanol, andembedded in Epon 812. Ultrathin sections were prepared,stained with uranyl acetate-lead citrate, and examinedusing a transmission electron microscope (JEOL 1010).Ultrastructurally paranuclear aggregates of intermediatefilaments were obtained (Fig. 5).

DISSCUSSION

Malignant rhabdoid tumor (MRT) was first describedby Beckwith and Palmer [3]. The term ‘‘rhabdoid tumor’’was recommended because of the lack of any evidence of

rhabdomyoblastic differentiation [4]. Extra-renal rhab-doid tumors are extremely rare. Sotelo-Avila et al. foundonly five among approximately 160,000 consecutivebiopsies to be extra renal MRT [2].

Extra-renal MRTs originate from a wide variety oftissues and organs including soft tissues, brain, liver,and bladder [1,2,5] but not find the adrenal prior to thisreport. The renal and extra-renal MRT share similar clinicand histopathologic features. They are generally seen ininfancy and early childhood and both have poor progno-sis. However, no association with brain tumors and extra-renal MRT has been reported in contrast to renal MRT[1,2,5].

Fig. 1. Mass located in left adrenal region extending to the para-aortic and retrocrural regions. Arrows mark the borders of tumor andthe arrow heads mark the medial border of kidney.

Fig. 2. In light microscopy non-cohesive pleomorphic neoplastic cellswith typical abundant eosinophilic cytoplasm are seen (H & E, 400�).

Fig. 3. Positive staining for vimentin as a discrete focus withincytoplasm (arrows). Note also the prominent nucleoli (200�).

Fig. 4. Cytoplasmic staining for epithelial membrane antigen is seen(200�).

Rhabdoid Tumor of Adrenal Gland 129

The typical histologic features include aggregatesof the so-called ‘‘rhabdoid’’ cells with eosinophiliccytoplasm containing filamentous cytoplasmic inclusionsand huge nucleoli.

In addition to the typical histologic features describ-ed above, the cells ultrastructurally contain characteristi-cally largemasses of intermediate filaments. Lack of thickand thin filaments, continuous basal lamina, neurosecre-tory granules, desmosomes, and well-developed celljunctions are the other findings. Immunohistochemicalfindings are variable, the usual being expression ofvimentin, epithelial membrane protein, and cytokeratin[1,2,4,5]. MRTs stained positively with S-100 protein,neuron-specific enolase, a1-antitrypsin have also beenreported [1,5]. Our case therefore has all the main histo-logic, ultrastructural, and immunohistochemical charac-teristics of the rhabdoid tumor albeit arising in theadrenal.

Recently a new tumor suppressor gene (INI1) onchromosome 22q11 was shown to be mutated in MRTs,especially in those located in the central nervous system[6]. Other abnormalities such as monosomy and atranslocation involving chromosome 22, translocationt(8;15)(q12;p11), and deletion 13q14 have also beenrecorded [7]. However, mutation of the INI-1 gene hasbeen observed in choroid plexus carcinomas, primitiveneuroectodermal tumors, and medulloblastomas too [8].Although the reported definitive diagnosis was MRT, insome cases an abnormality of chromosome 22 could notbe documented [9]. It is obvious that finding an abnormal

chromosome 22 supports the diagnosis, but is not specificfor the MRT. (We could not perform cytogenetics andmolecular analyses in our patient.)

Some tumors diagnosed as MRT of extrarenal sitesshared some morphologic characteristics of MRT ofthe kidney but had considerable clinical and laboratorydifferences. It was therefore recommended that extra-renal rhabdoid tumors that do not have the distinctiveclinical and pathologic features be called ‘‘pseudo-rhabdoid tumor’’ or ‘‘tumor with rhabdoid features’’:e.g., hepatoblastoma with rhabdoid features [1,6,10].

The unusual presentation site of our case calls for itsdifferentiation from neuroblastoma and adrenocorticalcarcinoma with rhabdoid features. The morphologic fea-tures of the tumor in our patient do not resemble thoseof neuroblastoma. Furthermore, immunohistochemically,neuroblastoma cells do not express epithelial markerssuch as cytokeratin and epithelial membrane antigen, andultrastructurally neurosecretory granules are seen [11].Adrenocortical carcinoma is a rare tumor of the adrenalcortex. There is a bimodal age distribution with the firstpeak occurring at age less than 5 years. In contrast toadult cases, most pediatric adrenocortical carcinomas arehormonally active. Virilization is the most common pre-sentation symptom [12]. Microscopically, adrenocorticalcarcinoma is generally similar to normal adrenal tissuein lower power, although morphologic features are notspecific on high magnification. Epithelial membrane anti-gen however is never positive in adrenocortical carci-noma [11]. Our patient did not have the symptoms of afunctional tumor and the epithelial membrane antigenwas positive, an important distinguishing feature.

There is a controversy regarding the histogenesisof MRT. In our case both epithelial and mesenchymalmarker were expressed. It has been proposed that extra-renal MRT may represent a heterogeneous group ofpoorly differentiated neoplasms with rhabdoid featureswhich have a different histogenesis in different organs[5,10].

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3. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilmstumour. Results from First National Wilms Tumor Study. Cancer1978;41:1937–1948.

4. Haas JE, Palmer NF, Weinberg AG, et al. Ultrastructure ofmalignant rhabdoid tumor of the kidney. A distinctive renal tumorof children. Hum Pathol 1981;12:646–657.

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Fig. 5. Electron microscopy of a cell showing paranuclear aggre-gates of intermediate filaments (Uranyl acetate lead citrate 6,000�).Arrow heads mark nuclear membrane and white darts mark aggregatesof intermediate filaments.

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8. Sevenet N, Lellouch-Tubiana A, Schofield D, et al. Spectrum ofhSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet 1999;8:2359–2368.

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